Inhibition of Spike Protein of SARS-CoV2 from (Merremia mammosa (Lour) Hall. F.) Bioactive Compounds: Molecular Docking and ADMET Study

Main Article Content

Neny Purwitasari
Saipul Maulana
Ema Qurnianingsih
Mangestuti Agil
Siswandono Siswandono
Jintana Junlatat

Keywords

Merremia mammosa (Lour), SARS-CoV2, Molecular docking, ADMET

Abstract

Spike protein is a receptor protein that has e role in the entry step of SARS-CoV2. This protein will bind to the ACE2 receptor in the human body and activate TMPRSS2. Inhibition of this protein will prevent the binding of the virus to host cells to spread the infection. This study aims to identify the activity of bioactive compounds of Merremia mammosa (Lour) tuber obtained from LC-MS/MS QTOF analysis of a previous study against the Spike protein of SARS-CoV2 using molecular docking and ADMET analysis. Molecular docking was conducted using SARS-CoV2 spike protein (PDB id. 6M0J) using Maestro Schrodinger software. Results showed that from 206 compounds there are 8 compounds of Merremia mammosa (Lour) that have lower predictive binding energies than standard drugs arbidol, hydroxychloroquine, and chloroquine. Result: 206 compounds of Merremia mammosa (Lour) tuber were successfully docked, there were 8 compounds that have docking scores more negative than standard drugs. It indicates that 8 compounds are more active than the positive controls. ADMET study revealed all of those potential ligands had the possibility to be developed as drugs. Conclusion: Molecular docking simulations were successfully utilized to identify the potential compounds from Merremia mammosa (Lour) tuber with the activity as an inhibitor for spike protein of SARS-CoV2. Further in vitro assay and purification are needed for future research.

Abstract 205 | PDF Downloads 275

References

1. Agil, M., Studiawan, H., & Purwitasari, N. (2021). Efficacy of Merremia mammosa Hall Terpenoid Fraction againts Mycobacterium tuberculosis. Research Journal of Pharmacy and Technology, 14(12). https://doi.org/10.52711/0974-360X.2021.01143
2. Choudhary, M. I., Shaikh, M., Atia-Tul-Wahab, & Atta-Ur-Rahman. (2020). In silico identification of potential inhibitors of key SARS-CoV-2 3CL hydrolase (Mpro) via molecular docking, MMGBSA predictive binding energy calculations, and molecular dynamics simulation. PLoS ONE, 15(7 July). https://doi.org/10.1371/journal.pone.0235030
3. Cyntia, V., & Widodo, A. (2012). Pengaruh Pemberian Ekstrak Daun Kumis Kucing (Orthosiphon aristatus) Terhadap Penurunan Kadar Glukosa Darah Tikus Wistar Yang Diinduksi Aloksan. Jurnal Kedokteran Diponegoro, 1(1), 112493.
4. de Almeida, S. M. V., Santos Soares, J. C., dos Santos, K. L., Alves, J. E. F., Ribeiro, A. G., Jacob, Í. T. T., da Silva Ferreira, C. J., dos Santos, J. C., de Oliveira, J. F., de Carvalho Junior, L. B., & de Lima, M. do C. A. (2020). COVID-19 therapy: What weapons do we bring into battle? Bioorganic and Medicinal Chemistry, 28(23). https://doi.org/10.1016/j.bmc.2020.115757
5. Farizal, J. (2012). Pengaruh Pemberian Ekstrak Etanol Umbi Bidara Upas (Merremia mammosa) Terhadap Proliferasi Limfosit dan Produksi Roi Makrofag Studi Eksperimental Infeksi Salmonella Typhimurium pada Mencit Balb/C. Diponegoro University.
6. Farooq, S., & Ngaini, Z. (2021). Natural and Synthetic Drugs as Potential Treatment for
Coronavirus Disease 2019 (COVID-2019). In Chemistry Africa (Vol. 4, Issue 1). https://doi.org/10.1007/s42250-020-00203-x
7. Friesner, R. A., Murphy, R. B., Repasky, M. P., Frye, L. L., Greenwood, J. R., Halgren, T. A., Sanschagrin, P. C., & Mainz, D. T. (2006). Extra precision glide: Docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. Journal of Medicinal Chemistry, 49(21). https://doi.org/10.1021/jm051256o
8. Genheden, S., & Ryde, U. (2015). The MM/PBSA and MM/GBSA methods to estimate ligand-binding affinities. In Expert Opinion on Drug Discovery (Vol. 10, Issue 5). https://doi.org/10.1517/17460441.2015.1032936
9. Hidayat, T. S. N. (2013). Peran Topikal Ekstrak Gel Aloe Vera pada Penyembuhan Luka Bakar derajat Dua Dalam. Universitas Airlangga.
10. Ikram, N. K. K., Durrant, J. D., Muchtaridi, M., Zalaludin, A. S., Purwitasari, N., Mohamed, N., Rahim, A. S. A., Lam, C. K., Normi, Y. M., Rahman, N. A., Amaro, R. E., & Wahab, H. A. (2015). A virtual screening approach for identifying plants with anti H5N1 neuraminidase activity. Journal of Chemical Information and Modeling, 55(2). https://doi.org/10.1021/ci500405g
11. Jadhav, R., & Puchchakayala, G. (2012). Hypoglycemic and antidiabetic activity of flavonoids: Boswellic acid, Ellagic acid, Quercetin, Rutin on streptozotocin-nicotinamide induced type 2 diabetic rats. International Journal of Pharmacy and Pharmaceutical Sciences, 4(2).
12. Julianto, I. G. P., Elfiah, U., & Sofiana, K. D. (2015). Pengaruh Pemberian Ekstrak Umbi Bidara Upas (Merremia mammosa (Lour)) terhadap Proses Penyembuhan Luka dan Kadar Gula Darah pada Tikus Wistar Jantan Hiperglikemi. Artikel Ilmiah Hasil Penelitian Mahasiswa, 1(1), 1.
13. Kitagawa, I., Baek, N. I., Yokokawa, Y., Yoshikawa, M., Ohashi, K., & Shibuya, H. (1996). Indonesian medicinal plants. XVI. Chemical structures of four new resin- glycosides, merremosides f, g, h1, and h2, from the tuber of Merremia mammosa (Convolvulaceae). Chemical and Pharmaceutical Bulletin, 44(9). https://doi.org/10.1248/cpb.44.1693
14. Madhavi Sastry, G., Adzhigirey, M., Day, T., Annabhimoju, R., & Sherman, W. (2013). Protein and ligand preparation: Parameters, protocols, and influence on virtual screening enrichments. Journal of Computer-Aided Molecular Design, 27(3). https://doi.org/10.1007/s10822-013-9644-8
15. Moradkhani, S., Farmani, A., Saidijam, M., & Taherkhani, A. (2021). COVID-19: docking-based virtual screening and molecular dynamics study to identify potential SARS-CoV-2 spike protein inhibitors from plant-based phenolic compounds. Acta Virologica, 65(3). https://doi.org/10.4149/av_2021_308
16. Olsson, M. H. M., Søndergaard, C. R., Rostkowski, M., & Jensen, J. H. (2011). PROPKA3: Consistent Treatment of Internal and Surface Residues in Empirical pKa Predictions BT - Journal of Chemical Theory and Computation. Journal of Chemical Theory and Computation, 7(2). https://doi.org/https://doi.org/10.1021/ct100578z
17. Olubiy, O. O., Olagunju, M., Keutmann, M., Loschwitz, J., & Strodel, B. (2020). High throughput virtual screening to discover inhibitors of the main protease of the coronavirus SARS-CoV-2. Molecules, 25(14). https://doi.org/10.3390/molecules25143193
18. Purwitasari, N., & Agil, M. (2022). Metabolite Profiling of Extract and Fractions of Bidara Upas (Merremia Mammosa (Lour.) Hallier F.) Tuber Using UPLC-QToF-MS/MS. Biomedical and Pharmacology Journal, 15(4). https://biomedpharmajournal.org/vol15no4/metabolite-profiling-of-extract-and-fractions-of-bidara-upas-merremia-mammosa-lour-hallier-f-tuber-using-uplc-qtof-msms/
19. Purwitasari, N., Agil, M., & Studiawan, H. (2020). Activity of ethyl acetate fraction of merremia mammosa hall as anti-influenza a
(H1N1). Indian Journal of Forensic Medicine and Toxicology, 14(3). https://doi.org/10.37506/ijfmt.v14i3.10734
20. Rutwick Surya, U., & Praveen, N. (2021). A molecular docking study of SARS-CoV-2 main protease against phytochemicals of Boerhavia diffusa Linn. for novel COVID-19 drug discovery. VirusDisease, 32(1). https://doi.org/10.1007/s13337-021-00683-6
21. Schrödinger Release 2022-1. (2022a). Desmond Molecular Dynamics System. LLC.
22. Schrödinger Release 2022-1. (2022b). Glide. LLC.
23. Schrödinger Release 2022-1. (2022c). Prime. LLC.
24. Schrödinger Release 2022-1. (2022d). Protein Preparation Wizard; Epik. LLC.
25. Sutrisno, D. E. (2014). Effect of Suspension of Bidara Upas (Merremia tuberosa (L) Rendle.) Powder on Blood Glucose Levels of Alloxan-Induced Wistar Male White Rats [Thesis]. : STIFAR. Sekolah Tinggi Ilmu Farmasi Semarang.
26. Zheng, J. (2020). SARS-coV-2: An emerging coronavirus that causes a global threat. International Journal of Biological Sciences, 16(10). https://doi.org/10.7150/ijbs.45053
27. Zubair, M. S., Maulana, S., Widodo, A., Pitopang, R., Arba, M., & Hariono, M. (2021). Gc-ms, lc-ms/ms, docking and molecular dynamics approaches to identify potential sars-cov-2 3-chymotrypsin-like protease inhibitors from zingiber officinale roscoe. Molecules, 26(17). https://doi.org/10.3390/molecules26175230